Background. Diffuse proliferative lupus nephropathy (DPLN) is the most frequent and severe form of renal disease in patients with systemic lupus erythaematosus. Histological parameters at the initial biopsy of patients with DPLN that would predict the progression of renal pathology or function at the second biopsy are not clearly defined. Methods. The prognostic significance of renal histological indices, such as glomerular activity index and volume density of cortical interstitium [Vv(int/cortex)]. was evaluated from successive renal biopsies in 21 patients with DPLN. Results. At the time of the second biopsies, performed an average of 43 months after the first biopsies, seven patients (33%) showed progressive renal insufficiency. Only three cases (14%) transformed to World Health Organization class I or III. The seven patients with clinical progression exhibited a higher frequency of hypertension, higher percent glomerulosclerosis, and larger Vv(int/cortex) at the time of second biopsy as compared with the 14 patients without renal insufficiency. At the first biopsy, patients with clinical progression showed a higher glomerular activity index (2.9 +/- 1.2 vs 1.3 +/- 0.8, P < 0.05) and larger Vv(int/ cortex (0.13 +/- 0.07 mu m(3)/mu m(3) vs 0.05 +/- 0.03 mu m(3)/mu m(3), P < 0.05) than the patients without progression. The glomerular activity index at the first biopsy correlated directly with per cent glomerulosclerosis, Vv(int/ cortex), and serum creatinine level at the second biopsy. Vv(int/cortex) in the first biopsy also showed a significant relation with per cent glomerulosclerosis and serum creatinine level at the second biopsy. Conclusions. These results suggest that higher glomerular activity and larger interstitial volume density at the initial biopsy can predict future progression of renal pathology or function in DPLN.